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Novel Protocol for Efficient Generation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Human Intestinal Organoids (HIOs)

By 11th February 2020No Comments

The following study was conducted by Scientists from Boston University and Boston Medical Center; Boston University School of Medicine; Cystic Fibrosis Foundation Therapeutics Lab, Lexington; Boston University School of Medicine, USA. Study is published in Nature Communications Journal as detailed below.

Nature Communications (2020); Volume:11, Article number: 215

Generation of Mesenchyme Free Intestinal Organoids from Human Induced Pluripotent Stem Cells


Efficient generation of human induced pluripotent stem cell (hiPSC)-derived human intestinal organoids (HIOs) would facilitate the development of in vitro models for a variety of diseases that affect the gastrointestinal tract, such as inflammatory bowel disease or Cystic Fibrosis. Here, we report a directed differentiation protocol for the generation of mesenchyme-free HIOs that can be primed towards more colonic or proximal intestinal lineages in serum-free defined conditions. Using a CDX2eGFP iPSC knock-in reporter line to track the emergence of hindgut progenitors, we follow the kinetics of CDX2 expression throughout directed differentiation, enabling the purification of intestinal progenitors and robust generation of mesenchyme-free organoids expressing characteristic markers of small intestinal or colonic epithelium. We employ HIOs generated in this way to measure CFTR function using cystic fibrosis patient-derived iPSC lines before and after correction of the CFTR mutation, demonstrating their future potential for disease modeling and therapeutic screening applications.


Nature Communications



Mithal, A., Capilla, A., Heinze, D. et al. Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells. Nat Commun 11, 215 (2020).